It is known that transamination reactions are performed by transaminases occurring widely in the biosphere. In practical terms, they play an important role in the biosynthesis of amino acids and intravital amines and are useful as synthetic means, but since these are enzyme reactions, there are significant limitations as regards the substrate, making it impossible to devise general reactions. However, in an article related to the fluorine-containing carbonyl compounds expressed by General Formula 1 below, Soloshonok at al. have recently reported that the corresponding aldimine can be obtained by subjecting an enamine obtained by reaction with benzylamine to a 1,3! proton shift reaction in the presence of an organic chlorine such as triethylamine. Following the publication of this article, it has been acknowledged that transamination reactions performed using the above reaction can be useful as a general method for synthesizing fluorine-containing amine compounds (Tetrahedron Lett., Vol. 35, No. 19, pp. 3119-3122, 1994; Tetrahedron, Vol. 52, No. 20, pp. 6953-6964, 1996; ibid., Vol. 52, No. 47, 14701-14712, 1996; Synlett., No. 9, pp. 919-921, 1996; J. Org. Chem., Vol. 61, No. 19, 6563-6569, 1996).
Transamination reactions performed using aminomethylpyridine are also reported at length in recently published patent literature. It has been accepted that such enzyme-like transamination reactions performed using 1,3! proton shift reactions can be widely used as general methods for synthesizing fluorine-containing amines. However, there is only one report concerning the use of (-)-cinchonidine in a method for performing such a 1,3! proton shift reaction by making use of asymmetric amines (Tetrahedron Lett., Vol. 35, No. 28, pp. 5063-5064, 1994), and no other information on the subject is known to exist. Demand for asymmetric fluorine-containing amines is strong because fluorine-containing amines are used as intermediates of drugs, agricultural chemicals, and reagents for determining optical purity. In the past, however, such amines were extremely expensive because they were obtained by optical resolution from racemic modifications. A need therefore existed for the development of a simple method for synthesizing fluorine-containing amines.
As a result of a painstaking effort involved in extensive research conducted under the conditions described above, aimed at developing an asymmetric transamination reaction in view of the aforementioned prior art, and centered on asymmetric (R)- or (S)-phenylethylamines, the inventors discovered that the target asymmetric transamination reactions can be conducted without initiating racemization by performing these reactions using an appropriate organic base as a solvent. The inventors devised the present invention on the basis of this discovery.